GOLD Suite Release Notes

 

Introduction

GOLD Suite Programs

Supported Platforms

Important Notices

New Features

Modifications

Bug Fixes

Support

 

Introduction

GOLD Suite is CCDC’s docking and post-processing software comprising GOLD 4.1, GoldMine 1.2 and Hermes 1.3. New Features, Modifications and Bug Fixes are listed in the sections below.

 

GOLD Suite Programs

•	Hermes: for 3D visualisation pre- and post-docking and interactive docking setup.

•	GOLD: for protein-ligand docking.

•	GoldMine: for post-processing of docking results.

 

Supported Platforms

GOLD Suite programs (Hermes, GOLD and GoldMine) are supported on the following platforms and operating systems:

 

•	Windows - Intel compatible, 32 bit Windows 2000/XP/Vista

•	Linux - Intel compatible, 32 bit (and 64 bit for GOLD):

•	RedHat Enterprise 4 & 5

•	SuSE Linux Enterprise [Desktop|Server] 10

•	Debian 4.0 Note: As we add support for newer versions of Linux, support for older versions may have to be withdrawn.

 

If you choose to use a version other than those listed above we cannot guarantee that the GOLD Suite will work correctly, although we will attempt to assist you with any problems you may encounter.

 

If you are interested in the GOLD Suite of programs for a different platform please contact support.

 

Important Notices

•

This GOLD Suite release sees the expansion of Hermes to act as a hub for many of CCDC's products: a client for Relibase+; a visualiser enabling interactive set-up of GOLD docking jobs and SuperStar runs; a socket for the GoldMine plug-in, enabling post processing of GOLD docking results. As such, a single GOLD Suite installation is now all that is required to gain access to all of this functionality, with the appearance and behaviour of Hermes depending on which current licences for CCDC products your organisation holds.

•	Access to GOLD 4.1 and GoldMine 1.2 is restricted in accordance with your current licence agreement. The visualisation features in Hermes version 1.3, however, can be utilised without registration. Hermes can therefore be installed on any machine and used on any machine at the site licensed.

•	Support for GOLD on Silicon Graphics will end on December 31st 2009. Linux supported platforms may be reviewed as we add support for later versions. Please refer to the CCDC website for the latest news on supported platforms.

•	The previous major release of GOLD (GOLD 4.0) was the last release to contain grommitt executables.

•	The GOLD Classic interface is no longer distributed.

•	Changes made to the GOLD API mean that user will need to recompile.

 

New Features

 

Hermes 1.3

•

An interface to SuperStar 2.0, for calculating interaction hotspots in protein active sites or around small molecules, is now available via Hermes 1.3. Further information on SuperStar can be found on CCDC’s website (http://www.ccdc.cam.ac.uk/products/life_sciences/superstar/) and further information on new features etc can be found in the SuperStar Release Notes (http://www.ccdc.cam.ac.uk/support/documentation/#superstar).

•	Hermes can now read fit_points.mol2 files generated by GOLD successfully. Read these files in via the GOLD, Load GOLD Fitting Points menu options in the main Hermes menu.

•	Complex selections that are no longer required can now be deleted via the Selection, Delete a Selection menu options in Hermes.

•	Protein structures can now be manually overlayed by pairwise selection of atoms or centroids from a reference protein and a similar protein.

•	Hermes now supports POVRay output (*.pov), http://www.povray.org/.

 

GOLD 4.1

•

A new scoring function, PLP (Piecewise Linear Potential) has been added (note that this is a beta feature). Further details about this scoring function can be found in the GOLD documentation and also in the following publication: Empirical Scoring Functions for Advanced Protein-Ligand Docking with PLANTS O. Korb, T. Stützle and T. E. Exner, J. Chem. Inf. Model., 49, 84-96, 2009 [DOI: 10.1021/ci800298z]

•	It is now possible to define flexible side chains with ChemScore, ASP and also PLP (previously flexible side chains could only be defined if using GoldScore).

•	Active site waters can now be toggled when scoring with ASP and PLP (previously this feature was restricted to GoldScore and ChemScore).

•

Flexible ring handling has been improved with the inclusion of ring template matching code. A ring template library derived from the Cambridge Structural Database (CSD) is provided in the GOLD distribution. If a match is found to any ligand rings, library conformations are used during the docking. It is possible for users to use their own ring template libraries.

•	GOLD configuration files can be set-up so that docking solutions are automatically rescored with another scoring function.

•	A per-atom score output option has been added so that individual atom contributions to the scoring function can be inspected.

•	Interaction motifs can now be defined to bias the docking towards solutions that form particular protein-ligand binding motifs. Motifs can be defined for protein H-bond donors, H-bond acceptors, lipophilic and CHO interactions.

•	Flexible docking runs can now be rescored with an alternate scoring function.

•	Virtual screening protocols are now provided for different protein target types.

•	A ligand reference file can now be specified in the ligand selection dialogue and if this is done, an RMSD is calculated for each solution, relative to the reference ligand. The calculated RMSD is available in ligand solution files and in the bestranking.lst file.

•	A utility, check_mol2.exe, is now provided in the utilities directory of the GOLD installation. This script uses the same algorithms as the main GOLD program to check the quality of the input ligand structure. Further details are provided in the GOLD documentation.

•	Histidine residues can now be flipped during docking. This option is activated via the Protonation & Tautomers widget in the GOLD front end.

 

GoldMine 1.2

•	Three new top level menu options (Main, Tools and Descriptors) have been added to the GoldMine Controller to assist with GoldMine DB analysis.

•

A new Data Explorer window has been added which is accessed through the Explore button in the Main GoldMine window. The Data Explorer window allows you to calculate descriptive statistics for descriptors and correlation matrices between descriptors. Histograms and scatterplots can also be generated. Accumulation and Receiver Operating Characteristic (ROC) curves can be viewed for any descriptors, if the database contains identified active and inactive ligands. A range of enrichment metrics (e.g. EF, AUC under ROC, BEDROC) can also be calculated.

•

Regression tools have been added under the GoldMine Main, Regression menu options that allow the best target specific analysis protocol for virtual screening to be established or for the construction of a 3D Quantitative Structure Activity Relationship (QSAR). Target specific scoring functions can be created.

•	A Choose Descriptors section has been added to the Descriptors tab of the GoldMine Controller. This enables GoldMine DB descriptors to be selected based on name, count, variance or absolute value.

•	Simple property descriptors such as Molecular weight, Donor atom count, Acceptor atom count, Rotatable bond count and Smiles string can be calculated for a particular GoldMine DB subset or for an entire DB. This feature is accessed via Descriptors, Simple properties....

•

Euclidean distances can be calculated for docking results. This is done by calculating a centroid in multi-dimensional space from a selection of solutions, then calculating a descriptor for the dataset representing their distance from that centroid. This feature is accessed via Descriptors, Distances....

•	Where per-atom scores have been output to GOLD docking results, these can be extracted into a GoldMine DB via Tools, Atom Energies....

•	If importing a *.mol2 or *.sdf file to a GoldMine DB, the option to standardise the molecule(s) to CSD conventions is offered.

•	Data from different dock sets can now be aggregated i.e. to create properties in one dockset from properties in another.

•

It is now possible to calculate hotspots for a selection of docked solutions. This feature allows for calculation of pharmacophore grids based on a selection of docked solutions. These so called hotspot grids can be visualised in Hermes and provide a means of visually observing average trends in the docking solutions. The hotspots can also be used to calculate new descriptors based on whether or not a docked solution has atom(s) of interest in the hotspot grids.

 

Modifications

•	In Hermes modified residues (e.g. HIE, a modified HIS residue) are now correctly handled as part of the protein rather than being denoted as a ligand.

•	To make use of the Start Picking and Stop Picking feature in Hermes it is now necessary to have a GoldMine DB loaded.

•	Protonation of arginine residues using the structure editing functionality in Hermes has been improved.

•	Some improvements have been made to the stereoviewing functionality in Hermes.

•	If setting up a docking from a raw PDB file, the GOLD GUI now forces you to save extracted ligand files to file. This is essential if the binding site is defined from the extracted ligand.

•	When defining a region constraint, the sphere can now be toggled on and off e.g. to allow selection of ligand atoms.

•	If automatic atom typing is switched on for proteins, Asn and Gln amide bonds typed as 1 are now retyped to am and are flipped. Note that if automatic atom typing is not switched on and Asn and Gln amide bonds are typed as 1, they will be rotated. Hermes now saves these bond types correctly as am.

•	New Library Screening, Virtual Screening, Default and Very Flexible buttons have been added to the Automatic GA Settings window to give a better guide to optimal speed settings for a given project.

•	A number of improvements have been made to the covalent constraint code.

•	Error reporting and handling has been improved when rescoring a concatenated SDF file.

•	GOLD now recognises S.O atom types as well as S.o.

•	The gold.params file can now be opened and saved from within the GOLD interface.

•	The way in which GoldMine is implemented in Hermes has changed meaning a number of menu options have changed location.

•	The GoldMine controller now has a slightly different appearance due to the incorporation of new features.

•	GoldMine DBs can be now be created for ligands only, without a protein being present.

•	Various usability improvements have been made to the Create GoldMine wizard.

 

Bug Fixes

•	In Hermes a bug to do with exporting poses and associated data twice has been fixed.

•	An issue to do with calculating descriptors for currently loaded docking solutions has been fixed.

•	Minimising the Hermes window no longer clears the atoms selected to be overlayed.

•	Hermes no longer crashes if a ligand atom coincident with scaffold atom is selected for a scaffold constraint.

•	Performance when viewing a multi-structure file has been improved in Hermes.

•	Protein files containing modified residues such as MSE (a modified MET residue) no longer cause Hermes to crash.

•	Problems with file offset values when running GOLD using PVM have been resolved.

•	The results from flexible docking runs can now be rescored successfully with GoldScore.

•	When running a docking containing active waters, the water barrier term, S(bar), is now included in all output files.

•	Several issues relating to the rotamer setup dialogue and deleting defined rotatable side chains have been fixed.

•	Problems in defining a constraint between a ligand and protein metal atom have been fixed.

•	An issue to do with the reading and writing of improper torsions (flexible side chains feature) has been corrected.

•	Error handling has been improved for scaffold substructures containing more atoms than the ligand being docked.

•	Arginine residues are now handled correctly (the guanidine moiety is kept in plane) when specified as fully flexible within the rotatable side chains dialogue.

•	GOLD jobs run from the interface can now use PVM.

•	The GOLD GUI now reports how many waters have been deleted.

•	Many improvements have been made to GoldMine dialogue windows.

•	GoldMine database creation now runs more quickly.

•	Issues to do with spreadsheet editing in GoldMine have been fixed.

 

Support

User guides for Hermes, GOLD and GoldMine are available from the CCDC website in HTML and PDF format:

http://www.ccdc.cam.ac.uk/support/documentation/

The GOLD configuration file gold.conf is also fully documented and can be found at the above page on our website.

 

Scientific and technical FAQs are also available from the CCDC website:

http://www.ccdc.cam.ac.uk/support/faqs_downloads/

 

If you require more information about these or any other matters concerning GOLD Suite, please contact CCDC User Support at:

 

Email: support@ccdc.cam.ac.uk

Tel: +44 1223 336022